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两种 Zika 病毒灭活候选疫苗可在小鼠中提供针对致死性挑战的保护。

Purified Inactivated Zika Vaccine Candidates Afford Protection against Lethal Challenge in Mice.

机构信息

Takeda Vaccines Inc, Cambridge, MA, USA.

Arboviral Diseases Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado, USA.

出版信息

Sci Rep. 2018 Nov 7;8(1):16509. doi: 10.1038/s41598-018-34735-7.

DOI:10.1038/s41598-018-34735-7
PMID:30405178
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6220238/
Abstract

In response to the 2016 global public health emergency of international concern announced by the World Health Organization surrounding Zika virus (ZIKV) outbreaks, we developed a purified inactivated Zika virus vaccine (PIZV) candidate from ZIKV strain PRVABC59, isolated during the outbreak in 2015. The virus isolate was plaque purified, creating six sub-isolated virus stocks, two of which were selected to generate PIZV candidates for preclinical immunogenicity and efficacy evaluation in mice. The alum-adjuvanted PIZV candidates were highly immunogenic in both CD-1 and AG129 mice after a 2-dose immunization. Further, AG129 mice receiving 2 doses of PIZV formulated with alum were fully protected against lethal ZIKV challenge and mouse immune sera elicited by the PIZV candidates were capable of neutralizing ZIKVs of both African and Asian genetic lineages in vitro. Additionally, passive immunization of naïve mice with ZIKV-immune serum showed strong positive correlation between neutralizing ZIKV antibody (NAb) titers and protection against lethal challenge. This study supported advancement of the PIZV candidate toward clinical development.

摘要

针对世界卫生组织宣布的 2016 年全球关注的寨卡病毒（ZIKV）疫情国际公共卫生紧急事件，我们从 2015 年疫情中分离的 ZIKV 株 PRVABC59 中开发了一种纯化的灭活寨卡病毒疫苗（PIZV）候选物。该病毒分离株经过蚀斑纯化，产生了 6 个亚分离病毒株，其中 2 个被选中用于生成 PIZV 候选物，以在小鼠中进行临床前免疫原性和疗效评估。在 CD-1 和 AG129 小鼠中，经过 2 剂免疫后，铝佐剂的 PIZV 候选物具有高度的免疫原性。此外，接受 2 剂用铝佐剂配制的 PIZV 免疫的 AG129 小鼠完全免受致死性 ZIKV 攻击的侵害，并且由 PIZV 候选物诱导的小鼠免疫血清能够中和体外的 ZIKV 非洲和亚洲遗传谱系。此外，用寨卡病毒免疫血清对幼稚小鼠进行被动免疫，显示中和寨卡病毒抗体（NAb）滴度与对致死性攻击的保护之间存在很强的正相关。这项研究支持将 PIZV 候选物推进到临床开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab78/6220238/4915c11b9301/41598_2018_34735_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab78/6220238/d7a3760fb9a5/41598_2018_34735_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab78/6220238/50fa59211b53/41598_2018_34735_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab78/6220238/26638387da5b/41598_2018_34735_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab78/6220238/4915c11b9301/41598_2018_34735_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab78/6220238/d7a3760fb9a5/41598_2018_34735_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab78/6220238/50fa59211b53/41598_2018_34735_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab78/6220238/26638387da5b/41598_2018_34735_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab78/6220238/4915c11b9301/41598_2018_34735_Fig4_HTML.jpg

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